63. Redistribution of ASIC1a channels triggered by the cytokine IL-6: Potential role of ASIC1a channels in neuroinflammation
Cytokines are essential modulators of the immune response; and Interleukin 6 (IL-6) is one of the main neuroinflammatory cytokines in the central nervous system (CNS). Both glial and neuronal cells express IL-6 and IL-6R (receptor) in the brain. CNS IL-6 is upregulated when neuroinflammation occurs, and IL-6 levels are increased in sera of Parkinson s, Huntington ´s as well as in animal models of these diseases. In addition, inflammation determines changes in metabolic activity and can result in acidosis. Changes in regional pH levels in the brain have been observed in a number of neurological and neurodegenerative disorders. ASIC (Acid sensing Ion) channels are sodium channels activated by tissue acidosis and thus become active in many pathological conditions. ASIC1 is the most abundant ASIC subunit in the mammalian central nervous system. Physiologically, its activation is related to synaptic plasticity, learning and memory. ASIC1 channels in particular permeate not only sodium but slightly calcium ions, and so can contribute to intracellular calcium levels and neuronal injury in pathological conditions. In fact, ASIC1 channels have been lately implicated in several neurological diseases, as
blocking this channel with ASIC1 toxin improves models of cerebral ischemia, Parkinson´s disease, Huntington´s and ALS. Therefore, we decided to analyze the role of IL-6 on ASIC1 channels. We studied dissociated mouse hippocampal cultures after 8-12 DIV (days in vitro) and HEK293t cells. We incubated the cultures with IL-6 (10 ng/ml 30 minutes) and did immunocytochemistry of the samples to detect ASIC1 and calcium sensitive dyes as a measure of ASIC1 activation. Our preliminary results show that IL-6 determines the redistribution of a cytosolic pool of ASIC1 channels to the membrane of the neurons, and an increase in ASIC1 currents. These results point at a mechanism by which neuroinflammation could contribute to neurodegeneration; and ASIC1 as a potential target to aim at in these conditions.